Biomedical subjects
Jean-Marie Parel
Publications and source records attributed to Jean-Marie Parel.
Noncontact optical measurement of lens capsule thickness in human, monkey, and rabbit postmortem eyes.
PURPOSE: To measure interspecies thickness differences in the central anterior and posterior capsules of postmortem crystalline lenses, by a technique that maintains the anatomic integrity of the lens. METHODS: Central capsule thickness was measured with a custom-built, noncontact optical system, using a focus detection technique. Anterior and posterior lens capsule thickness measurements were performed on 22 human, 29 monkey, and 34 New Zealand White rabbit intact postmortem lenses in situ. Eyes were prepared for optical measurements by bonding a PMMA ring to the sclera in the region of the ciliary body after the conjunctiva, adipose, and muscle tissues were removed. The posterior pole was removed by making a circumferential incision through the sclera approximately 7 mm posterior to the limbus. Excess vitreous was removed to expose the posterior capsule surface, and the eye assembly was placed on a Teflon slide. The cornea and iris were sectioned to expose the anterior capsule surface. After the experiments, the lenses were excised, placed in 10% buffered formalin, and prepared for histology. Lens capsule thickness was measured from the histologic slides and compared to the optical RESULTS: results. Central anterior lens capsule thickness was 8.2 +/- 5.5 (human), 7.5 +/- 4.4 (monkey), and 10.7 +/- 4.2 (rabbit) microm optically and 12.4 +/- 2.5 (human), 10.7 +/- 3.7 (monkey), and 10.4 +/- 2.0 (rabbit) microm histologically. Central posterior capsule thickness was 6.3 +/- 2.2 (human), 5.9 +/- 1.7 (monkey), and 7.8 +/- 2.3 (rabbit) microm optically and 4.1 +/- 1.5 (human), 3.5 +/- 1.6 (monkey), and 4.7 +/- 2.5 (rabbit) microm histologically. CONCLUSIONS: The central anterior and posterior lens capsule thicknesses do not appear to vary considerably among human, rabbit, and monkey eyes. There were significant differences between optical in situ measurements and histology, which indicates that histologic preparation may affect lens capsule thickness.
The heterogeneous murine corneal stromal cell populations in vitro.
PURPOSE: To demonstrate that the murine corneal stroma is inhabited by heterogeneous cell populations that include cells expressing nestin. METHODS: Collagenase-isolated corneal stroma cells obtained from newborn and adult mice (2nd and 12th postnatal weeks, respectively), were seeded at low (5 cells/mm2), intermediate (50 cells/mm2), and high (500 cells/mm2) densities in DMEM/F12 containing insulin, transferrin, selenium, and 1% nonessential amino acids. Corneal stroma cells cultured at 500 cells/mm2 were treated with 10 ng/mL human recombinant transforming growth factor (TGF)-beta1 for 5 days. Cell morphology and expression of alpha-smooth muscle actin, choline acetyltransferase, CD45, glial fibrillary acidic protein (GFAP), keratocan, nestin, neurofilaments, protein gene product 9.5, tyrosine hydroxylase, and vimentin were examined. RESULTS: Phase-contrast microscopy demonstrated that freshly isolated corneal stromal cells are heterogeneous in morphology and include dendritic, stellate, neuronal, and small polyhedral cells. Immunostaining of primary cultures of 2- and 12-week-old mice, 24 hours after seeding at the intermediate density, showed that 100% of cells expressed vimentin and 97.7% +/- 2.7% expressed keratocan. alpha-Smooth muscle actin was expressed by 0.2% +/- 0.05% of cells in the 2-week-old group and 0.1% +/- 0.07% in 12-week-old group. Neurofilament was expressed by 0.5% +/- 0.03% and 0.7% +/- 0.03% of cells in the 2- and 12-week-old groups, respectively. No cell expressed GFAP or nestin. After 5 days in culture, cells seeded at high density aggregated as clusters that were immunoreactive to nestin in both groups. Cell clusters and migrating cells reacted to pgp 9.5, and migrating cells, but not the cell clusters, reacted to tyrosine hydroxylase. Cell cluster formation and nestin expression were abolished by culturing in the presence of TGF-beta1. CONCLUSIONS: Normal murine corneal stroma contains heterogeneous cell populations including cells with the potential to form clusters and express the progenitor marker nestin. This potential is disrupted by the addition of TGF-beta1 to the culture medium.
Thermal analysis of laser interstitial thermotherapy in ex vivo fibro-fatty tissue using exponential functions.
A therapeutic procedure to treat small, surface breast tumours up to 10 mm in radius plus a 5 mm margin of healthy, surrounding tissue using laser interstitial thermotherapy (LITT) is currently being investigated. The purpose of this study is to analyse and model the thermal and coagulative response of ex vivo fibro-fatty tissue, a model for breast tissue, during experimental laser interstitial thermotherapy at 980 nm. Laser radiation at 980 nm was delivered interstitially through a diffusing tip optical fibre inserted into a fibro-fatty tissue model to produce controlled heating at powers ranging from 3.2 to 8.0 W. Tissue temperature was measured with thermocouples placed at 15 positions around the fibre. The induced coagulation zone was measured on gross anatomical sections. Thermal analysis indicates that a finite sum of exponential functions is an approximate solution to the heat conduction equation that more accurately predicts the time-temperature dependence in tissue prior to carbonization (T < 100 degrees C) during LITT than the traditional model using a single exponential function. Analysis of the ellipsoid coagulation volume induced in tissue indicates that the 980 nm wavelength does not penetrate deep enough in fibro-fatty tissue to produce a desired 30 mm diameter (14.1 x 10(3) mm3) coagulation volume without unwanted tissue liquefaction and carbonization.
Biological response to a supraDescemetic synthetic cornea in rabbits.
OBJECTIVE: To evaluate the biocompatibility of a novel nonpenetrating keratoprosthesis (supraDescemetic synthetic cornea) in a rabbit model. METHODS: Seven rabbits received a supraDescemetic synthetic cornea (7-mm diameter, 350-microm-thick optical zone, 100-microm-thick peripheral flange) in their healthy right eyes. A surgical technique was developed that allowed implantation of the device on top of the bare Descemet membrane. Three rabbits received a supraDescemetic synthetic cornea made of hydroxyethyl methacrylate-methyl methacrylate(26), 1 received a hydroxyethyl methacrylate-N-vinyl pyrrolidone(75) mesoplant, and 3 were implanted with devices made of polymethyl methacrylate. All rabbits were euthanized after 8 weeks; the eyes were enucleated and examined by conventional histological and immunohistochemical evaluations. RESULTS: All eyes became quiet within several days. The Descemet membrane remained transparent during the observation period. Indirect ophthalmoscopy performed through the prosthesis allowed accurate examination of the posterior pole. Histological evaluation of the implanted corneas displayed no signs of an acute or chronic inflammatory reaction to the supraDescemetic synthetic cornea in 5 eyes; a few inflammatory cells were detected in the corneas of 2 rabbits. The interface between the Descemet membrane and the mesoplant displayed ingrowth of very thin (<10-microm) tissues colonized by keratocytes in 3 of the 7 corneas. CONCLUSIONS: This study validates the biocompatibility of this new type of nonpenetrating keratoprosthesis. Because opening of the anterior chamber is not required with the supraDescemetic synthetic cornea, the risk for intraocular infection is minimal, and the implantation procedure is less traumatic compared with a penetrating device.
Efficacy of various drugs in the prevention of posterior capsule opacification: experimental study of rabbit eyes.
PURPOSE: To assess the efficacy of various drugs in the prevention of posterior capsule opacification (PCO) in a closed capsular bag technique. SETTING: Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida, USA. METHODS: Lens material was removed using phacoaspiration or phacoemulsification through a microcapsulorhexis according to the hardness of the crystalline lens correlated with the weight and age of the rabbits. A mixture of an ophthalmic viscosurgical device (sodium hyaluronate 1.4% [SHA]) and a drug was injected into the empty capsular bag, allowed to remain inside for 3 minutes, and removed. The capsular bag was rinsed with balanced salt solution (BSS) and refilled with SHA. In a group of rabbits, the capsulorhexis was sealed with a minicapsulorhexis valve (MCV). Rabbits were treated with 1 of the following: SHA (control), BSS, mitomycin-C (MMC, 0.2 mg/mL), ethylenediaminetetraacetic acid (EDTA) (10 mM and 15 mM), 5-fluorouracil (5-FU, 33 mg/mL), acetic acid (3%, 0.3%, and 0.003%), and distilled water. RESULTS: Upon completion of the study, the control and treated eyes had PCO and new lens material (not residual). Anterior capsule proliferation was observed in eyes treated with 5-FU. The order of PCO appearance (earliest to latest) was as follows: 15 mM EDTA, SHA, MMC, acetic acid 0.3%, acetic acid 3%, BSS, distilled water (small animals; no MCV), acetic acid 0.003%, 5-FU, 10 mM EDTA, and distilled water (large animals; MCV). The earliest appearance was day 1 postoperatively and the latest, day 47. CONCLUSIONS: Distilled water and 10 mM EDTA treatments were the most efficient in retarding the appearance of PCO.
Preparation and hydration control of corneal tissue strips for experimental use.
PURPOSE: The purpose of this study was to develop an experimental protocol to maintain corneal tissue strips at normal hydration and avoid swelling or dehydration during experimental studies on corneal biomechanics and thermal stability. METHODS: The corneal thickness of 9 whole Eye-Bank eyes was brought back to normal values by immersion in a 25% dextran solution for 24 hours. Corneal buttons were then removed and cut into 2 x 6 mm strips. The 9 strips were immersed successively in Dextran solutions at 25%, 22.5%, and 20% concentration at 35 degrees C. The thickness of the immersed strip in solution was measured every 5 minutes for 1 hour using a modified optical comparator. RESULTS: The mean final thickness for the nine corneal strips after one hour in 25%, 22.5%, and 20% dextran solution was 508 +/- 38, 563 +/- 56, and 592 +/- 33 microm, respectively. Average swelling in 25%, 22.5%, and 20% dextran solutions was 1.06 +/- 0.03, 1.20 +/- 0.07, and 1.24 +/- 0.07 times the initial thickness, respectively. CONCLUSION: The hydration of corneal tissue strips is maintained at normal values when the strips are immersed in 25% Dextran solution. Corneal strips swell to thicknesses above normal values in solutions with lower molecular weights.
Pharmacokinetics of systemic versus focal Carboplatin chemotherapy in the rabbit eye: possible implication in the treatment of retinoblastoma.
PURPOSE: To characterize the pharmacology and toxicity of intravenous versus focal carboplatin delivery in the rabbit eye. METHODS: Pharmacological distribution of carboplatin was examined in New Zealand White Rabbits after a single intravenous infusion of carboplatin (18.7 mg/kg of body weight), a single subconjunctival carboplatin injection (5.0 mg/400 microL), or a single application of carboplatin delivered by Coulomb-controlled iontophoresis (CCI; 14 mg/mL carboplatin, 5.0 mA/cm(2), 20 minutes). After each treatment, animals were euthanatized, and the eyes analyzed at 1, 2, 6, or 24 hours by atomic absorption spectroscopy to determine carboplatin concentration in ocular structures. Potential toxicity of focally delivered carboplatin was assessed by histology after six cycles of 5.0 mg carboplatin delivered by subconjunctival injection or six transscleral carboplatin CCI applications at 72-hour intervals (14.0 mg/mL, 20 minutes at 2.5 mA). RESULTS: Determination of concentrations through atomic absorption spectroscopy in the retina, choroid, vitreous humor, and optic nerve after subconjunctival injection or iontophoretic carboplatin delivery revealed significantly higher levels than those achieved with intravenous administration. Carboplatin concentrations in the blood plasma were found to be significantly higher after intravenous delivery than after focal delivery by subconjunctival injection or CCI. No evidence of ocular toxicity was detected after focally delivered Carboplatin. CONCLUSIONS: Focal administration of carboplatin using subconjunctival or noninvasive CCI safely and effectively transmits this chemotherapeutic drug into the target tissues of the retina, choroid, vitreous, and optic nerve. These results suggest that focal carboplatin delivery may effectively increase intraorbital carboplatin concentrations while decreasing systemic exposure to this cytotoxic drug.
Semianalytical thermal model for subablative laser heating of homogeneous nonperfused biological tissue: application to laser thermokeratoplasty.
We present a semianalytical technique to calculate the temperature in homogeneous nonperfused tissue during subablative laser heating. Analytical expressions of the temperature distribution in time and space are provided for collimated beams with Gaussian and top-hat intensity distributions perpendicularly incident on a finite tissue slab. The temperature distribution produced with a collimated Gaussian beam is the triple sum of the product of four functions of separate variables. The semianalytical technique can be used to rapidly calculate the temperature in laser-irradiated tissue at any point in time and space. The model was used to estimate the corneal temperature during pulsed holmium:YAG laser thermokeratoplasty with various boundary conditions at the anterior and posterior corneal surface. The model demonstrates that the corneal temperature during laser thermokeratoplasty (LTK) with a pulsed Ho:YAG laser may be sufficient to induce superficial vaporization of epithelial cells and local thermal damage to the endothelium. The calculations show that convection at the anterior corneal surface does not have a significant effect on the corneal temperature distribution, but that a better knowledge of the cooling effect of the aqueous is required to better estimate the corneal temperature distribution during LTK.
Laser interstitial thermotherapy (LITT) monitoring using high-resolution digital mammography: theory and experimental studies.
Laser interstitial thermotherapy (LITT) is a minimally-invasive laser hyperthermia procedure for the treatment of localized tumours. Real-time monitoring of LITT is essential to control the extent of tumour destruction and ensure safe and effective treatments. The feasibility of using high-resolution digital x-ray mammography to monitor LITT of breast cancer was evaluated. Tissue phantoms including polyacrylamide hydrogel and cadaver porcine tissue were heated using a 980 nm diode laser delivered through optical fibres with diffusing tips. Digital images of the tissue phantoms were recorded with a high-resolution digital stereotactic breast biopsy system during heating. The recorded images were processed and analysed to detect heat-induced changes. No changes were detected during heating of the hydrogel. Pixel-by-pixel subtraction of the initial image from images taken during laser heating shows observable thermally-induced changes around the fibre during laser irradiation that correlate with the thermal denaturation zone observed by gross anatomy. These experiments demonstrate that high-resolution digital x-ray mammography can be used to detect heat-induced tissue changes during experimental LITT in fibro-fatty tissue.
Ablation profiles for wavefront-guided correction of myopia and primary spherical aberration.
PURPOSE: To calculate ablation profiles for wavefront-guided correction of ametropia and primary spherical aberration. SETTING: Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA. METHODS: The primary spherical aberrations of the ocular surfaces of an aspheric eye model were calculated before and after simulated ablations for correction of myopia ranging from 0 to 10 diopters. The corneal asphericity to correct primary spherical aberration and the corresponding ablation profiles were also calculated. RESULTS: The corneal asphericity factor that produces zero primary spherical aberration ranges from -0.45 to -0.47. The calculated ablation profiles are parabolic in first approximation, and the ablation depth varies linearly with the amount of correction. To control residual primary spherical aberration with a tolerance of one-quarter wavelength, the precision of the ablation must range from 0.2 to 0.3 microm. CONCLUSIONS: Ocular aberrometry and corneal topography can be used to calculate ablations for the correction of ametropia and primary spherical aberration. Precise control of postoperative spherical aberration appears to be feasible in theory.
Ocular aspirin distribution: a comparison of intravenous, topical, and coulomb-controlled iontophoresis administration.
PURPOSE: To evaluate the pharmacokinetics and safety of aspirin delivered by a single, noninvasive, transscleral, coulomb-controlled iontophoresis (CCI) treatment; topical application; or by one intravenous (IV) injection. METHODS: Forty-one adult New Zealand White rabbits received either a single IV injection, topical, or CCI administration of aspirin at a concentration of 10 mg/mL. Histologic evaluation was performed in four CCI-treated eyes to assess safety. Pharmacokinetic distribution in all ocular tissues and fluids was studied at 0.5, 1, 2, 4, 6, and 8 hours after the treatments. Immediately after death, the eyes were dissected and salicylic acid (SA) concentration was determined by HPLC analysis. Blood was sampled at 0.5, 1, 2, 4, 6, and 8 hours, and plasma SA levels for systemic distribution were measured by HPLC analysis. RESULTS: No tissue damage was observed clinically or histologically. SA was found in all tissues and fluids throughout the study period of 8 hours. The highest concentrations of SA were observed with CCI immediately after treatment for all tissues and were the highest SA tissue peaks obtained by the studied delivery methods. IV administration demonstrated a delayed tissue peak of salicylate at 2 hours after administration. At 8 hours, ocular SA concentrations were in the same range for CCI and IV administration. IV injection resulted in blood plasma levels up to 28 times higher than CCI and remained significantly elevated until 8 hours after the treatments. CONCLUSIONS: CCI is a safe and effective method of administering aspirin to the eye while avoiding the systemic side effects associated with IV injection.
Toward a miniaturized fundus camera.
Retinopathy of prematurity (ROP) describes a pathological development of the retina in prematurely born children. In order to prevent severe permanent damage to the eye and enable timely treatment, the fundus of the eye in such children has to be examined according to established procedures. For these examinations, our miniaturized fundus camera is intended to allow the acquisition of wide-angle digital pictures of the fundus for on-line or off-line diagnosis and documentation. We designed two prototypes of a miniaturized fundus camera, one with graded refractive index (GRIN)-based optics, the other with conventional optics. Two different modes of illumination were compared: transscleral and transpupillary. In both systems, the size and weight of the camera were minimized. The prototypes were tested on young rabbits. The experiments led to the conclusion that the combination of conventional optics with transpupillary illumination yields the best results in terms of overall image quality.
Ocular delivery of acetylsalicylic acid by repetitive coulomb-controlled iontophoresis.
To investigate the potential of transscleral coulomb-controlled iontophoresis (CCI) for repetitive delivery of acetylsalicylic acid (ASA) into the eye, a total of 50 rabbits was included in this study. Fourteen animals received serial CCI treatment. Fourteen animals underwent CCI with either ASA or balanced salt solution (BSS) for at least 6 days at 24- and 48-hour intervals. Eighteen animals received a single CCI application, while 18 animals were injected with 15 mg ASA/kg body weight intravenously. HPLC analysis was performed to determine the levels of salicylic acid (SA) in ocular tissues. Apart from clinical follow-up, 2 rabbits in the ASA and BSS groups were examined by electroretinography, and 2 animals were examined histologically. Though high concentrations of SA were measured, no alterations were observed clinically, histologically and electrophysiologically. Repetitive CCI demonstrated its potential as a topical drug delivery system for ASA into the eye. This transscleral delivery of ASA resulted in significant and sustained intraocular concentrations of SA without side effects. Iontophoresis may be advantageous in clinical administration maintaining therapeutic levels of ASA while avoiding adverse effects associated with the systemic administration of nonsteroidal anti-inflammatory drugs.
Ultraviolet corneal photoablation.
PURPOSE: The purpose of this article is to discuss missing information on the basic physical and biological processes of ultraviolet corneal photoablation and to evaluate its potential clinical implications. METHODS: A physical description of ultraviolet laser corneal ablation that includes photothermal, photochemical, and radiative processes is proposed. RESULTS: Unresolved issues include the nature of the primary ablation process, the tissue and biological effects of the photothermal and photochemical components of the interaction, and the static and dynamic absorption process. CONCLUSIONS: A better understanding of the basic physics and biology of ultraviolet corneal photoablation may help us better understand, predict, and perhaps minimize the effect of tissue hydration, plume formation, and other factors that affect the predictability of ablation and the induced tissue damage.
Internal sclerostomy with the Er:YAG laser using a gradient-index (GRIN) endoscope.
BACKGROUND AND OBJECTIVE: To show that sclerostomy, a glaucoma filtering surgery, can be performed using an Er:YAG laser. Scarring at the filtering site, a recurrent problem, may be reduced through proper positioning of the sclerostomy by using an intraocular endoscope. MATERIALS AND METHODS: Ab interno full-thickness sclerostomies were performed on eye bank eyes with an Er:YAG laser through a custom made optical delivery system. The intraocular laser probe consisted of a low OH silica fiber inserted in a metallic tapered sheathing. A rigid intraocular endoscope based on gradient-index lenses allowed visualization of the filtration site. RESULTS: A clear view of the anterior chamber angle was obtained through the endoscope, allowing for precise location of the sclerostomy. Full-thickness sclerostomies could then be performed at the desired location. Histologic sections showed thermal necrosis less than 50 microm thick in tissue adjacent to the sclerostomy. CONCLUSIONS: A sclerostomy performed with a combined procedure using an Er:YAG laser and intraocular endoscopy increases the speed of the procedure. The use of a high-resolution intraocular endoscope may increase the success rate of ab interno laser glaucoma surgeries.
Trabecular meshwork alteration and intraocular pressure change following pulsed near-infrared laser trabeculoplasty in cats.
BACKGROUND AND OBJECTIVE: To comparatively assess the safety and variation in intraocular pressure (IOP) of two pulsed near-infrared lasers (titanium:sapphire and alexandrite) for laser trabeculoplasty versus conventional blue-green argon laser trabeculoplasty in an animal model. MATERIALS AND METHODS: The left eyes of 15 healthy cats received a 180 degree laser trabeculoplasty treatment: 5 with a titanium:sapphire laser, 5 with an alexandrite laser, and 5 with an argon laser. Preoperatively and postoperatively, all animals underwent tonometry, gonioscopy, and slit-lamp examination. The cats were observed up to 12 weeks. Scanning electron microscopy and histologic examination were performed to evaluate potential alterations in the trabecular meshwork structure. RESULTS: IOP at 1 hour, 1 day, and 1 week following treatment was remarkably lower, irrespective of the laser source used. Following treatment with both near-infrared lasers, gonioscopy showed depigmentation underneath the area of the treated trabecular meshwork and histologic evaluation showed a decrease in pigment density. On scanning electron microscopy, damage to the trabecular meshwork structure could not be detected after treatment with near-infrared lasers. CONCLUSIONS: Near-infrared laser trabeculoplasty was found to be effective to temporarily lower IOP in cats. The lasers selectively altered pigment-containing cells, avoiding structural damage of the trabecular meshwork anatomy.